NR3C1Glucocorticoid receptor

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06537"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25775514"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "27120390"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28139699"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "37478846"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9590696"
        }
      ],
      "value": "Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity)"
    }
  ],
  "commentType": "FUNCTION"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06537"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11435610"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15769988"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17635946"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19141540"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19248771"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20484466"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21664385"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23303127"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23820903"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25847991"
        }
      ],
      "value": "Has transcriptional activation and repression activity (PubMed:11435610, PubMed:15769988, PubMed:15866175, PubMed:17635946, PubMed:19141540, PubMed:19248771, PubMed:20484466, PubMed:21664385, PubMed:23820903). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity)"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06537"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19248771"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20484466"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "26711253"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "7769088"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8621628"
        }
      ],
      "value": "Acts as a dominant negative inhibitor of isoform Alpha (PubMed:20484466, PubMed:7769088, PubMed:8621628). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253)"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Beta"
}

{
  "texts": [
    {
      "value": "Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466)"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11358809"
        }
      ],
      "value": "Increases activity of isoform Alpha"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform GR-P"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11435610"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "More effective than isoform Alpha in transcriptional activation, but not repression activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-B"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20484466"
        }
      ],
      "value": "Has transcriptional activation activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform 10"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Has transcriptional activation activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-C1"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Has transcriptional activation activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-C2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23303127"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23820903"
        }
      ],
      "value": "Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903)"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-C3"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Has transcriptional activation activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-D1"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Has transcriptional activation activity"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-D2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23303127"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23820903"
        }
      ],
      "value": "Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127)"
    }
  ],
  "commentType": "FUNCTION",
  "molecule": "Isoform Alpha-D3"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11238589"
        }
      ],
      "value": "High constitutive expression by neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death and up-regulation by pro-inflammatory cytokines such as IL8 further enhances their survival in the presence of glucocorticoids during inflammation"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Beta"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10639135"
        }
      ],
      "value": "Can up- or down-modulate aggregation and nuclear localization of expanded polyglutamine polypeptides derived from AR and HD through specific regulation of gene expression. Aggregation and nuclear localization of expanded polyglutamine proteins are regulated cellular processes that can be modulated by this receptor, a well-characterized transcriptional regulator"
    }
  ],
  "commentType": "MISCELLANEOUS"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Predominant physiological form"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Due to a partial intron retention"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Due to a partial intron retention"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Beta-2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8358712"
        }
      ],
      "value": "Lacks exons 5, 6 and 7. Found in glucocorticoid-resistant myeloma patients"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform GR-A alpha"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8358712"
        }
      ],
      "value": "Lacks exons 5, 6 and 7"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform GR-A beta"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8358712"
        }
      ],
      "value": "Encoded by exons 2-7 plus several basepairs from the subsequent intron region. Lacks the ligand binding domain. Accounts for up to 10-20% of mRNAs"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform GR-P"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Produced by alternative initiation at Met-27 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-B"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        },
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Produced by alternative initiation at Met-27 of isoform Beta"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Beta-B"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-86 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-C1"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-90 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-C2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-98 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-C3"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-316 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-D1"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-331 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-D2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15866175"
        }
      ],
      "value": "Produced by alternative initiation at Met-336 of isoform Alpha"
    }
  ],
  "commentType": "MISCELLANEOUS",
  "molecule": "Isoform Alpha-D3"
}

Eukaryota → Metazoa → Chordata → Craniata → Vertebrata → Euteleostomi → Mammalia → Eutheria → Euarchontoglires → Primates → Haplorrhini → Catarrhini → Hominidae → Homo

{
  "names": {
    "recommendedName": {
      "fullName": {
        "value": "Glucocorticoid receptor"
      },
      "shortNames": [
        {
          "value": "GR"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "Nuclear receptor subfamily 3 group C member 1"
        }
      }
    ]
  },
  "genes": [
    {
      "geneName": {
        "evidences": [
          {
            "evidenceCode": "ECO:0000312",
            "source": "HGNC",
            "id": "HGNC:7978"
          }
        ],
        "value": "NR3C1"
      },
      "synonyms": [
        {
          "value": "GRL"
        }
      ]
    }
  ]
}

{
  "commentType": "DISEASE",
  "disease": {
    "diseaseId": "Glucocorticoid resistance, generalized",
    "diseaseAccession": "DI-04226",
    "acronym": "GCCR",
    "description": "An autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of Cushing syndrome typical signs. Clinical features include hypoglycemia, hypertension, metabolic alkalosis, chronic fatigue and profound anxiety.",
    "diseaseCrossReference": {
      "database": "MIM",
      "id": "615962"
    },
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "11589680"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "11701741"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12050230"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "15769988"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "1704018"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "17635946"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "20335448"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "21362280"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "23426617"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "24483153"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "26031419"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "26541474"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "27120390"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "7683692"
      }
    ]
  },
  "note": {
    "texts": [
      {
        "value": "The disease is caused by variants affecting the gene represented in this entry"
      }
    ]
  }
}

{
  "texts": [
    {
      "value": "Carriers of the 22-Glu-Lys-23 allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than non-carriers, resulting in a better metabolic health profile. Carriers have a better survival than non-carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males"
    }
  ],
  "commentType": "POLYMORPHISM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19141540"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21980503"
        }
      ],
      "value": "Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11435610"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11555652"
        }
      ],
      "value": "Increased proteasome-mediated degradation in response to glucocorticoids (PubMed:11555652). Isoform Alpha-B appears to be more susceptible to proteolytic degradation than isoform Alpha (PubMed:11435610)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06537"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12000743"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18483179"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18838540"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25847991"
        }
      ],
      "value": "Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoid. The Ser-203, Ser-226 and Ser-404-phosphorylated forms are mainly cytoplasmic, and the Ser-211-phosphorylated form is nuclear (PubMed:12000743, PubMed:18838540). Phosphorylation at Ser-211 increases transcriptional activity (PubMed:12000743, PubMed:18483179). Phosphorylation at Ser-203, Ser-226 and Ser-404 decreases signaling capacity (PubMed:12000743, PubMed:18483179, PubMed:18838540). Phosphorylation at Ser-404 may protect from glucocorticoid-induced apoptosis (PubMed:18838540). Phosphorylation at Ser-203 and Ser-211 is not required in regulation of chromosome segregation (PubMed:25847991). May be dephosphorylated by PPP5C, attenuates NR3C1 action (By similarity)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "37478846"
        }
      ],
      "value": "Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound NR3C1 when it is not associated with coactivators (NCOAs) (PubMed:37478846). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (PubMed:37478846)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06536"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12144530"
        }
      ],
      "value": "Sumoylation at Lys-277 and Lys-293 negatively regulates its transcriptional activity (PubMed:12144530). Sumoylation at Lys-703 positively regulates its transcriptional activity in the presence of RWDD3 (By similarity). Sumoylation at Lys-277 and Lys-293 is dispensable whereas sumoylation at Lys-703 is critical for the stimulatory effect of RWDD3 on its transcriptional activity (By similarity). Heat shock increases sumoylation in a RWDD3-dependent manner (By similarity)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10902803"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25847991"
        }
      ],
      "value": "Widely expressed including bone, stomach, lung, liver, colon, breast, ovary, pancreas and kidney (PubMed:25847991). In the heart, detected in left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole adult and fetal heart (PubMed:10902803)"
    }
  ],
  "commentType": "TISSUE SPECIFICITY"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "7769088"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8621628"
        }
      ],
      "value": "Widely expressed including brain, bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, skeletal muscle, heart, placenta and blood leukocytes"
    }
  ],
  "commentType": "TISSUE SPECIFICITY",
  "molecule": "Isoform Beta"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10566686"
        }
      ],
      "value": "Widely expressed"
    }
  ],
  "commentType": "TISSUE SPECIFICITY",
  "molecule": "Isoform Alpha-2"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11381138"
        }
      ],
      "value": "Induced by TNF (at protein level)"
    }
  ],
  "commentType": "INDUCTION",
  "molecule": "Isoform Alpha"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11381138"
        }
      ],
      "value": "Induced by TNF and becomes the predominant isoform which may lead to glucocorticoid resistance (at protein level)"
    }
  ],
  "commentType": "INDUCTION",
  "molecule": "Isoform Beta"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06536"
        },
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P06537"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10477749"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10866662"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12151000"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12686538"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15211577"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15591535"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15769988"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15941832"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16478993"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16914116"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17635946"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18838540"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19141540"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20078863"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21730050"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21980503"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22170608"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25775514"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "27353360"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28139699"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "29127155"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9154805"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9353307"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9590696"
        }
      ],
      "value": "Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:21730050). Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes its place, thereby linking the complex to dynein and mediating transport to the nucleus, where the complex dissociates (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Directly interacts with UNC45A (PubMed:16478993). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (By similarity). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (PubMed:10866662, PubMed:12151000, PubMed:12686538, PubMed:9154805, PubMed:9590696). Interaction with BAG1 inhibits transactivation (PubMed:10477749). Interacts with HEXIM1 and TGFB1I1 (PubMed:12415108, PubMed:15211577, PubMed:15941832). Interacts with NCOA1 (PubMed:9590696). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (PubMed:19141540, PubMed:21980503, PubMed:22170608). Interacts with CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (PubMed:15769988, PubMed:17635946). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (PubMed:15591535). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (PubMed:25775514). Interacts with GSK3B (PubMed:18838540). Interacts with FNIP1 and FNIP2 (PubMed:27353360). Interacts (via C-terminus) with HNRNPU (via C-terminus) (PubMed:9353307). Interacts with MCM3AP (PubMed:16914116). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). Interacts (via NR LBD domain) with ZNF764 (via KRAB domain); the interaction regulates transcription factor activity of NR3C1 by directing its actions toward certain biologic pathways (PubMed:28139699)"
    }
  ],
  "commentType": "SUBUNIT"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25847991"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "3841189"
        }
      ],
      "value": "Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain (PubMed:3841189). The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required (PubMed:25847991)"
    }
  ],
  "commentType": "DOMAIN"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305"
        }
      ],
      "value": "Belongs to the nuclear hormone receptor family. NR3 subfamily"
    }
  ],
  "commentType": "SIMILARITY"
}

Alternative splicing · Alternative initiation

{
  "commentType": "ALTERNATIVE PRODUCTS",
  "events": [
    "Alternative splicing",
    "Alternative initiation"
  ],
  "isoforms": [
    {
      "name": {
        "value": "Alpha"
      },
      "synonyms": [
        {
          "value": "Alpha-A"
        },
        {
          "value": "GR-alphaA"
        }
      ],
      "isoformIds": [
        "P04150-1"
      ],
      "isoformSequenceStatus": "Displayed"
    },
    {
      "name": {
        "value": "Beta"
      },
      "synonyms": [
        {
          "value": "Beta-A"
        }
      ],
      "isoformIds": [
        "P04150-2"
      ],
      "sequenceIds": [
        "VSP_003703"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-2"
      },
      "synonyms": [
        {
          "value": "Gamma"
        }
      ],
      "isoformIds": [
        "P04150-3"
      ],
      "sequenceIds": [
        "VSP_007363"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Beta-2"
      },
      "isoformIds": [
        "P04150-6"
      ],
      "sequenceIds": [
        "VSP_007363",
        "VSP_003703"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "GR-A alpha"
      },
      "isoformIds": [
        "P04150-5"
      ],
      "sequenceIds": [
        "VSP_013340"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "GR-A beta"
      },
      "isoformIds": [
        "P04150-7"
      ],
      "sequenceIds": [
        "VSP_013340",
        "VSP_003703"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "GR-P"
      },
      "isoformIds": [
        "P04150-4"
      ],
      "isoformSequenceStatus": "Not described"
    },
    {
      "name": {
        "value": "Alpha-B"
      },
      "synonyms": [
        {
          "value": "GR-alphaB"
        }
      ],
      "isoformIds": [
        "P04150-8"
      ],
      "sequenceIds": [
        "VSP_018773"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Beta-B"
      },
      "isoformIds": [
        "P04150-9"
      ],
      "sequenceIds": [
        "VSP_018773",
        "VSP_003703"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "10"
      },
      "synonyms": [
        {
          "value": "hGRDelta313-338"
        }
      ],
      "isoformIds": [
        "P04150-10"
      ],
      "sequenceIds": [
        "VSP_043908"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-C1"
      },
      "synonyms": [
        {
          "value": "GR-alphaC1"
        }
      ],
      "isoformIds": [
        "P04150-11"
      ],
      "sequenceIds": [
        "VSP_058317"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-C2"
      },
      "synonyms": [
        {
          "value": "GR-alphaC2"
        }
      ],
      "isoformIds": [
        "P04150-12"
      ],
      "sequenceIds": [
        "VSP_058316"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-C3"
      },
      "synonyms": [
        {
          "value": "GR-alphaC3"
        }
      ],
      "isoformIds": [
        "P04150-13"
      ],
      "sequenceIds": [
        "VSP_058315"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-D1"
      },
      "synonyms": [
        {
          "value": "GR-alphaD1"
        }
      ],
      "isoformIds": [
        "P04150-14"
      ],
      "sequenceIds": [
        "VSP_058314"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-D2"
      },
      "synonyms": [
        {
          "value": "GR-alphaD2"
        }
      ],
      "isoformIds": [
        "P04150-15"
      ],
      "sequenceIds": [
        "VSP_058313"
      ],
      "isoformSequenceStatus": "Described"
    },
    {
      "name": {
        "value": "Alpha-D3"
      },
      "synonyms": [
        {
          "value": "GR-alphaD3"
        }
      ],
      "isoformIds": [
        "P04150-16"
      ],
      "sequenceIds": [
        "VSP_058312"
      ],
      "isoformSequenceStatus": "Described"
    }
  ]
}

• P04150-1 · Alpha · Displayed · Alpha-A, GR-alphaA
  Complete source annotation

  {
    "name": {
      "value": "Alpha"
    },
    "synonyms": [
      {
        "value": "Alpha-A"
      },
      {
        "value": "GR-alphaA"
      }
    ],
    "isoformIds": [
      "P04150-1"
    ],
    "isoformSequenceStatus": "Displayed"
  }

• P04150-2 · Beta · Described · Beta-A · VSP_003703
  Complete source annotation

  {
    "name": {
      "value": "Beta"
    },
    "synonyms": [
      {
        "value": "Beta-A"
      }
    ],
    "isoformIds": [
      "P04150-2"
    ],
    "sequenceIds": [
      "VSP_003703"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-3 · Alpha-2 · Described · Gamma · VSP_007363
  Complete source annotation

  {
    "name": {
      "value": "Alpha-2"
    },
    "synonyms": [
      {
        "value": "Gamma"
      }
    ],
    "isoformIds": [
      "P04150-3"
    ],
    "sequenceIds": [
      "VSP_007363"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-6 · Beta-2 · Described · VSP_007363, VSP_003703
  Complete source annotation

  {
    "name": {
      "value": "Beta-2"
    },
    "isoformIds": [
      "P04150-6"
    ],
    "sequenceIds": [
      "VSP_007363",
      "VSP_003703"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-5 · GR-A alpha · Described · VSP_013340
  Complete source annotation

  {
    "name": {
      "value": "GR-A alpha"
    },
    "isoformIds": [
      "P04150-5"
    ],
    "sequenceIds": [
      "VSP_013340"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-7 · GR-A beta · Described · VSP_013340, VSP_003703
  Complete source annotation

  {
    "name": {
      "value": "GR-A beta"
    },
    "isoformIds": [
      "P04150-7"
    ],
    "sequenceIds": [
      "VSP_013340",
      "VSP_003703"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-4 · GR-P · Not described
  Complete source annotation

  {
    "name": {
      "value": "GR-P"
    },
    "isoformIds": [
      "P04150-4"
    ],
    "isoformSequenceStatus": "Not described"
  }

• P04150-8 · Alpha-B · Described · GR-alphaB · VSP_018773
  Complete source annotation

  {
    "name": {
      "value": "Alpha-B"
    },
    "synonyms": [
      {
        "value": "GR-alphaB"
      }
    ],
    "isoformIds": [
      "P04150-8"
    ],
    "sequenceIds": [
      "VSP_018773"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-9 · Beta-B · Described · VSP_018773, VSP_003703
  Complete source annotation

  {
    "name": {
      "value": "Beta-B"
    },
    "isoformIds": [
      "P04150-9"
    ],
    "sequenceIds": [
      "VSP_018773",
      "VSP_003703"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-10 · 10 · Described · hGRDelta313-338 · VSP_043908
  Complete source annotation

  {
    "name": {
      "value": "10"
    },
    "synonyms": [
      {
        "value": "hGRDelta313-338"
      }
    ],
    "isoformIds": [
      "P04150-10"
    ],
    "sequenceIds": [
      "VSP_043908"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-11 · Alpha-C1 · Described · GR-alphaC1 · VSP_058317
  Complete source annotation

  {
    "name": {
      "value": "Alpha-C1"
    },
    "synonyms": [
      {
        "value": "GR-alphaC1"
      }
    ],
    "isoformIds": [
      "P04150-11"
    ],
    "sequenceIds": [
      "VSP_058317"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-12 · Alpha-C2 · Described · GR-alphaC2 · VSP_058316
  Complete source annotation

  {
    "name": {
      "value": "Alpha-C2"
    },
    "synonyms": [
      {
        "value": "GR-alphaC2"
      }
    ],
    "isoformIds": [
      "P04150-12"
    ],
    "sequenceIds": [
      "VSP_058316"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-13 · Alpha-C3 · Described · GR-alphaC3 · VSP_058315
  Complete source annotation

  {
    "name": {
      "value": "Alpha-C3"
    },
    "synonyms": [
      {
        "value": "GR-alphaC3"
      }
    ],
    "isoformIds": [
      "P04150-13"
    ],
    "sequenceIds": [
      "VSP_058315"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-14 · Alpha-D1 · Described · GR-alphaD1 · VSP_058314
  Complete source annotation

  {
    "name": {
      "value": "Alpha-D1"
    },
    "synonyms": [
      {
        "value": "GR-alphaD1"
      }
    ],
    "isoformIds": [
      "P04150-14"
    ],
    "sequenceIds": [
      "VSP_058314"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-15 · Alpha-D2 · Described · GR-alphaD2 · VSP_058313
  Complete source annotation

  {
    "name": {
      "value": "Alpha-D2"
    },
    "synonyms": [
      {
        "value": "GR-alphaD2"
      }
    ],
    "isoformIds": [
      "P04150-15"
    ],
    "sequenceIds": [
      "VSP_058313"
    ],
    "isoformSequenceStatus": "Described"
  }

• P04150-16 · Alpha-D3 · Described · GR-alphaD3 · VSP_058312
  Complete source annotation

  {
    "name": {
      "value": "Alpha-D3"
    },
    "synonyms": [
      {
        "value": "GR-alphaD3"
      }
    ],
    "isoformIds": [
      "P04150-16"
    ],
    "sequenceIds": [
      "VSP_058312"
    ],
    "isoformSequenceStatus": "Described"
  }

• UniProt / The UniProt Consortium ↗ · 2026-11-09T11:39:40.193503+00:00
• InterPro / EMBL-EBI and the member sources identified in the annotations ↗ · 2026-11-09T11:39:40.086034+00:00
• AlphaFold DB / DeepMind Technologies Limited / EMBL-EBI ↗ · 2026-11-09T11:39:41.770639+00:00
• UniProt / The UniProt Consortium ↗ · 2026-11-09T11:39:40.193503+00:00
• InterPro / EMBL-EBI and the member sources identified in the annotations ↗ · 2026-11-09T11:39:40.086034+00:00
• AlphaFold DB / DeepMind Technologies Limited / EMBL-EBI ↗ · 2026-11-09T11:39:41.770639+00:00
• UniProt overview ↗ · 2026-11-10T20:42:44.745182+00:00
• www.ebi.ac.uk ↗ · 2026-11-10T21:11:27.591671+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:27.600435+00:00
• www.ebi.ac.uk ↗ · 2026-11-10T21:11:27.633410+00:00
• omabrowser.org ↗ · 2026-11-10T21:11:27.677123+00:00
• omabrowser.org ↗ · 2026-11-10T21:11:27.723035+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:28.223807+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:28.251727+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:29.177639+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:29.219281+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:30.259183+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:30.449629+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:31.195371+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:31.368383+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:32.251777+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:32.267652+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:33.286093+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:33.289538+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:34.162250+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:35.329721+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:36.391673+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:37.226533+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:37.257270+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:38.339606+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:38.378467+00:00
• rest.uniprot.org ↗ · 2026-11-10T21:11:38.407628+00:00